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Protein crown around nanoparticles: Size matters!

​When immersed in biological media, nanoparticles are immediately "wrapped" in proteins. A study conducted by researchers from the Iramis and Joliot (I2BC) institutes clarifies the importance of protein size on the formation of this envelope and recommends better consideration of this parameter in proteomic and nanotoxicological studies.

Published on 3 March 2021

The use of nanoparticles is widespread in nanomedicine, notably for in vivo diagnosis, targeted drug delivery or molecular imaging.

When a nanoparticle is injected into a biological medium such as blood or mucus, it is instantly covered with proteins adsorbed on its surface, which give it a specific "biological identity". This protein "crown" (corona) can condition the bio-distribution as well as the possible toxicity of the nanoparticle.  

Many factors can influence the composition and structure of the adsorbed protein layers. Among these, the size of the proteins, whose importance in the composition and structure of the corona has been suggested by several clues, had never been specifically explored.

In this study, the researchers chose to observe the interactions between silica nanoparticles of homogeneous size with proteins of the hemoprotein family whose size alone varied by a factor of 10. They deployed a battery of techniques: adsorption isotherms, isothermal titration calorimetry, circular dichroism and cryo transmission electron microscopy. Result: the adsorption mechanisms of small and large proteins are totally distinct!

Small proteins form homogeneous monolayers on the surface of nanoparticles thanks to chemical recognition processes, possibly adapting their structure. Large proteins, whose size is of the order of that of the nanoparticles, tend to form incomplete coronas. They can also bind to several nanoparticles, leading to more open arrangements, retaining multiple degrees of freedom.

The formation of the protein corona, studied in this work as a function of a single variable, the size of the proteins, does influence the aggregation of silica nanoparticles, thus conditioning their distribution in living organisms and natural environments.

This work was carried out by two Iramis teams - from NIMBE (Nanosciences and Innovation for Materials, Biomedicine and Energy) and the Léon Brillouin Laboratory, both UMR CEA-CNRS - and researchers from the Institute of Integrative Cell Biology (I2BC, UMR CNRS-CEA-Université Paris-Saclay).

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